“Time-resolved cryo-EM reveals mechanism of allosteric activation in isocitrate lyase 2”

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Date and Time

4:00 PM – 5:30 PM Friday, September 26^th, 2025

Location

Hybrid (Zoom and KEK CryoEM building)

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Speakers : Ghader Bashiri

Associate Professor
Laboratory of Microbial Biochemistry and Biotechnology
School of Biological Sciences, The University of Auckland

Abstract

Allostery is a fundamental regulatory mechanism underpinning many biochemical and physiological processes within cells. Allostery occurs when a binding event at one site on a protein affects binding at a remote functional site, thereby enabling precise control of enzymatic function. Isocitrate lyase 2 (ICL2) serves as a regulatory hub in the central metabolism of Mycobacterium tuberculosis, the bacterium that causes tuberculosis, where is modulates carbon flux in the central carbon metabolism.

Our crystal structures of Mtb-ICL2 demonstrate that binding of acetyl-CoA or propionyl-CoA at a site distant to the active site induces extensive conformational changes, leading to a ~100-fold increase in its enzymatic activity. Using time-resolved cryo-EM, we captured the trajectory of these structural transitions, from a time point as early as 150 ms through to the fully active state. Our data reveal the dynamic population shifts between protein conformations over time. Our findings provide unprecedented insights into the mechanisms underlying allosteric activation of Mtb-ICL2.

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“医学はアート？〜サイエンスに基づく臨床の思考プロセスに触れる〜”

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Date and Time

2025年8月29日（金）　10:00

Location

オンサイト（構造生物棟会議室）

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Speakers:

戒能 賢太

筑波大学　医学医療系　内分泌代謝・糖尿病内科

Abstract

構造生物学を含むあらゆる生物学研究の中でも、特に哺乳類を対象とした研究は、臨床応用を目的とすることが多いかと思います。研究成果に基づく診断ツールとしての検査法の開発や、新たな治療法の創出は比較的イメージしやすく、実際に日々新しい検査法や治療法が臨床の場で応用されており、医学は常に進歩を遂げていると言えます。しかし「検査」や「治療」といった選択肢は、患者さんが病院を訪れてから何らかの転帰に至るまでの過程全体の中ではあくまで一部分に過ぎず、実際、臨床医の思考の多くは適切な検査や治療を選択するまでのプロセスに費やされています。医学教育の礎を築いたウィリアム・オスラーは、そのプロセスを指して「医学とは、科学に基づく技術（アート）である」と表現しましたが、今回のセミナーでは、医学が対象とする領域の中でもそうした「アート的」側面に焦点を当て、その一端に触れていただければと思います。

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“DeepMASC: Automated Mask Creation and Class Selection in Single Particle Analysis Empowered by Deep Protein Probability Measures of Cryo-EM Maps”

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Date and Time

4:00 PM – 5:30 PM Monday, June 16^th, 2025

Location

Hybrid (Zoom and KEK SBRC building)

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Speakers:

Mr. Han Zhu, M.S.

Department of Computer Science, Purdue University, US.

Abstract

We have developed DeepMASC (Deep Masking and Auto-Selection for Classifications), a novel approach that eliminates human intervention from two critical steps in the cryo-EM single particle analysis (SPA) computational workflow: 3D class selection and 3D reference mask generation. Our method leverages deep learning-based protein probability measures to automatically identify optimal structural classes and generate appropriate masks for further refinement. DeepMASC dramatically accelerates the SPA workflow by eliminating time-consuming manual interventions that often create significant delays. Traditional workflows require expert decisions at critical junctures, creating bottlenecks that can extend processing time from hours to days. By automating these decision points, DeepMASC enables continuous, uninterrupted processing without sacrificing quality.
To address broader computational challenges in cryo-EM analysis, we also have developed the Kihara Lab EMSuite Server, a free and comprehensive web platform offering 13 algorithms for cryo-EM analysis. The server spans the full spectrum of needs, from secondary structure detection at medium resolution to atomic modeling at high resolution for proteins, nucleic acids, and their complexes. This unified interface makes sophisticated cryo-EM analysis accessible to structural biologists regardless of computational expertise, democratizing access to cutting-edge methods without requiring specialized hardware or software installation.

Profile

2018-2022              B.S., Department of Computer Science, Purdue University, US.

2022-2023              M.S., Department of Computer Science, Purdue University, US.

2023-Present          Ph.D. program, Department of Computer Science, Purdue University, US

Research Focus

Computational Structural Biology, ML-Based Cryo-EM Modeling and Analysis

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“Tracking molecular motions in proteins using conventional and advanced X-ray crystallography techniques”

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Date and Time

4:00 PM – Wednesday, May 21, 2025

Location

Hybrid (Zoom and KEK CryoEM building)

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Speakers:

Swagatha Ghosh

Designated Assistant Professor, Department of Applied Physics, Nagoya

University (Japan)

Abstract

X-ray crystallography remains one of the most widely used and well-established structural biology techniques for obtaining high-resolution, atomic-level structures of macromolecules. While most X-ray crystallography proteins structures till date emerge from single crystals shot at cryogenic temperatures, and automation techniques have immensely increased their utilization, these conventional methods have certain drawbacks. Requirement of large crystals and screening for suitable cryo-protectants could limit structural studies of proteins at physiologically relevant conditions and triggering reaction for real-time dynamical information. Recently, advancements of serial X-ray crystallography techniques with micro-focused beams and faster detectors have allowed structure determination from (sub)micron- sized crystals at room-temperature and deciphering molecular mechanisms triggered with light or chemical stimulus. This technology hence allows generating ‘molecular movies’ by capturing different transient states of a protein’s reaction cycle.
In my talk, I will give an overview of my research on several soluble and membrane protein systems with exciting properties and utilization of various X-ray crystallography techniques for elucidating their molecular mechanisms. Briefly, I will discuss about 1) my on-going project on deciphering photo- physical mechanisms of large spectral shift fluorescent proteins from blue fish, 2) several past projects on membrane proteins associated with bioenergetics in cells and 3) design and development sample-delivery devices for in situ and serial crystallography that could be implemented in any synchrotron radiation facility. The goal of my presentation is to promote a simpler approach for sample preparation and data-collection that could lower the entry barrier for novice users for X-ray crystallography at synchrotrons.

Presenter’s bio

Swagatha Ghosh is a structural biologist with keen interest in macromolecular biophysics of proteins using conventional and advanced X-ray crystallography and UV-VIS spectroscopy. She had completed her PhD in Bangalore, India and postdoctoral research in Gothenburg, Sweden. Using conventional- and serial- crystallography techniques, her research aims at deciphering structural mechanisms in proteins. She has co-founded a deep-tech startup in Sweden aiming to develop sample
delivery techniques for serial crystallography. She moved to Nagoya University (Japan) in August 2022, as Designated Assistant Professor to pursue her research on fluorescent proteins (FP). In addition to her research, she teaches experimental biophysics to undergrad students and is actively involved in building networking platforms for international researchers at Nagoya University.

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“The structure, dynamics and function of Adaptive Immune Receptors ”

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Date and Time

4:00 PM – 5:30 PM Friday, May 9^th, 2025

Location

Hybrid (Zoom and KEK CryoEM building)

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Speakers:

Daron Standley, PhD

Research Institute for Microbial Diseases (RIMD), Osaka University (Professor)

Abstract

Adaptive immune receptors (AIRs) consist of B cell receptors (BCRs)—also known as antibodies in their soluble form—and T cell receptors (TCRs), which remain anchored to the plasma membrane of T cells. AIRs are unique among human proteins in that they are generated by the combinatorial assembly of genes, leading to an extraordinary diversity of expressed proteins that undergo positive and negative selection throughout our lives. The diversity is so great that any two humans typically share only a few percent of their BCRs or TCRs in a routine blood draw. In spite of this incredible diversity, different individuals respond to vaccines in much the same way within days—a remarkable example of robustness and functional convergence. I will describe one particularly interesting example of convergent responses that, unexpectedly, enhances SARS-CoV-2 infection. I will also show how BCR and TCR sequencing of peripheral blood can be used to diagnose a wide range of diseases, including infections, autoimmunity, and cancer. If time permits, I will also introduce a model of how T cells sense antigens—derived from unbiased molecular dynamics simulations and validated experimentally.

Profile

1998–2003: Schrödinger, Inc. (New York, USA) — Scientific Software Developer
Engaged in the development of scientific software, including flexible docking.

2003–2008: Osaka University, Institute for Protein Research, Protein Data Bank Japan (PDBj) — Senior Researcher
Developed tools for structure-based searching  at PDBj.

2008–2014: Osaka University, Immunology Frontier Research Center (IFReC) — Specially Appointed Associate Professor
Launched the systems immunology lab where I worked on modeling immune responses.

2014–2016: Kyoto University, Institute for Virus Research — Professor
Developed tools for high-throughput BCR and TCR modeling.

2014–Present: Osaka University, Research Institute for Microbial Diseases, Division of Genome Informatics — Professor
I worked in disease diagnosis using adaptive immune receptors.

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“SBCloud: A Cloud-based Platform for Cryo-EM Structure Determination and Training from SBGrid”

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Date and Time

4:00 PM – 5:30 PM Wednesday, April 16^th, 2025

Location

Hybrid (Zoom and KEK CryoEM building)

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Speakers:

Jason Key, PhD

Associate Director of Technology & Innovation, SBGrid Consortium Lecturer on Biological Chemistry and Molecular Pharmacology,
Harvard Medical School

　　

Abstract

The ever-growing demand for computational power, data storage, and access to cutting-edge scientific software can be a formidable challenge for structural biology research labs. SBGrid, an international research computing consortium based at Harvard Medical School aims to break down technological barriers in structural biology and accelerate discoveries. To support this mission, SBGrid provides an extensive suite of scientific software, expert domain-specific support, computing hardware solutions, and training for scientists investigating molecular mechanisms at the atomic level. Recognizing the increasing computational demands of cryo-EM structure determination, we developed SBCloud—an AWS infrastructure-as-code high-performance computing environment designed for advanced analysis and visualization of structural biology data. We have used SBCloud to host global cryo-EM workshops, fostering collaboration and hands-on training in high-performance computing for structural biologists. We recently offered SBCloud to the SBGrid community on a limited basis, enabling researchers to tackle cryo-EM and Cryo-ET structure determination projects and enabling us to test our platform at scale. In this presentation, I will share insights and lessons learned from our experience in training and supporting the global cryo-EM and Cryo-ET research community and discuss the role of cloud resources in computational structural biology.

　　

Profile

1997 BS Biochemistry
Purdue University, West Lafayette, IN, USA

2004 Ph.D, Time-resolved Laue diffraction of Bacterial sensor proteins
University of Chicago, Chicago IL, USA

2004-2007, Postdoc, Femtosecond laser spectroscopy of sensor proteins
Free University Amsterdam/University of Amsterdam, Netherlands

2007-2012, Postdoc, Inhibition of HIF-2alpha with small molecules
University of Texas Southwestern, TX USA

2012-2014, Structural Biology Computing Specialist, Harvard
2014-current, Lecturer on Biological Chemistry and Molecular Pharmacology
2014-current, Associate DIrector of Technology and Innovation, SBGrid Consortium

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“Structural Biology in Industry – Proteros overview”

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Date and Time

5:00 PM – 6:30 PM Wednesday, January 22^th, 2025

Location

Online (Zoom)

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Speakers:

Eva Cunha, PhD

Profile:
2006 Master (Bioinformatics), University of Lisbon, Portugal
2013 Ph.D. (Biophysics), Jonhs Hopkins University, USA
2013-2015 Postdoctoral Researcher with Dr. N. Abrescia, CIC-Biogune, Spain
2016-2018 Postdoctoral Researcher with Dr. W. Kuhlbrandt, Max-Planck-Institute for Biophysics, Germany
2018-2021 Researcher, University of Oslo, Norway
2021-2022 Principal Investigator, University of Oslo, Norway
2022-2023 Director for cryoEM, Proteros Biostructures, Germany
2024-Present Department Head and BU co-head for cryoEM, Proteros Biostructures, Germany

Stephan Krapp, PhD

Profile:
1997 Master of Biochemistry, Imperial College, UK / University of Bayreuth, Germany
2002 Ph.D. in Protein Crystallography, Max-Planck-Institute of Biochemistry, Martinsried, Germany (Prof. Dr. Robert Huber)
2003 Research scientist and project manager at Proteros Biostructures, Martinsried, Germany
2010 Department Head of Structural Biology at Proteros Biostructures, Martinsried, Germany
2022 – present: Business Unit Head x-ray crystallography and co-Department head x-ray crystallography at Proteros Biostructures, Martinsried, Germany

Abstract

Proteros offers cutting-edge cryo-electron microscopy (cryoEM) and x-ray crystallography services tailored to accelerate drug discovery by providing high-resolution structural insights into challenging pharmaceutical targets. Our platform integrates state-of-the-art cryoEM and x-ray instrumentation, proprietary workflows, and deep expertise in structure determination to deliver actionable data for small-molecule and biologics programs.

Proteros specializes in resolving protein structures, protein-ligand complexes, and multi-protein assemblies with precision, even for challenging targets like membrane proteins. By enabling atomic resolution insights, our services empower researchers to drive structure-based drug design, optimize lead compounds, and elucidate mechanisms of action. This talk will highlight Proteros’ streamlined processes, success stories, and how our structural biology capabilities bridge the gap between molecular structures and therapeutic breakthroughs. Case studies will include GPCR´s (e.g. GLP1R), ion channels (e.g. Kv.1.3) Kinases (e.g. TAK1, cRAF-14-3-3) and others.

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